1. Field of the Invention
This invention relates to blood containers and to multiple blood bag systems for collecting processing and storage of blood and blood components under sterile conditions. Further objects of the invention will be evident from the following description wherein parts and percentages are by weight unless otherwise specified.
2. Description of the Prior Art
For a number of years, blood has been collected and processed into various components such as packed red cells, plasma platelets and cryoprecipitate, using a system comprising two or more plastic bags interconnected by tubing. The blood is first collected from a donor into a primary or donor bag to which is connected one or more secondary or satellite bags. Both the donor and satellite bags have been routinely made of polyvinyl chloride (PVC) film containing as plasticizer di-2-ethylhexyl phthalate (DEHP).
For some time, however, it has been known that considerable amounts of DEHP are leached from the walls of the blood bags by the plasma in the blood when blood or packed red cells are stored for long periods of time. There has been concern over the potentially harmful effects of DEHP on patients repeatedly infused with blood or blood components even though there appears to be no significant toxicity based on animal studies.
Consequently, we have tested numerous plastic formulations in an attempt to find acceptable material for blood bags which would be flexible, translucent, steam sterilizable and contain a low level of leachable plasticizers. The material should also have properties which are not detrimental to the components of blood; for example, the material should not cause undue hemolysis of red cells or decrease the viability of platelets upon storage to levels which would be clinically unacceptable.
It was shown very early that the commercially available blood bags, which were made of PVC plasticized with DEHP, were generally better than glass containers for the long term storage of blood. Strumia et al (J. Lab. and Clin. Med. 46, 225, 1955) demonstrated that hemolysis was less and post transfusion survival of the red cells was improved for blood stored in these plastic bags. This inherent property of PVC bags plasticized with DEHP has contributed to this being until recently the only material for blood bags which was and still is acceptable and approved by Government regulatory agencies for storage of red blood cells. It has been theorized that this condition of decreased hemolysis of red cells is attributable to the DEHP (or dioctyl adipate) which is extracted from the bag by the blood and that the DEHP inhibits hemolysis (U.S. Pat. No. 4,222,379, hereinafter '379).
Platelet concentrates are routinely obtained by well established procedures from blood plasma and are stored in medical grade polyvinyl chloride (PVC) bags at about 22.degree. C. prior to use.
Platelet concentrates contain glucose (dextrose) as a consequence of the process by which they are collected since the blood has been collected in bags containing buffered anticoagulants such as ACD (acid citrate-dextrose) or CPD (citrate-phosphate-dextrose). During storage, the platelets convert glucose to lactic acid and carbon dioxide (CO.sub.2) which lower the pH. Murphy and Gardner (Blood, Vol. 46, No. 2, pp. 209-218, 1975) measured CO.sub.2 and oxygen pressures in various PVC and polyethylene (PE) bags containing platelet concentrates and observed that the drop in pH was greater the thicker the walls of the bag. Since oxygen is known to suppress conversion of glucose to lactic acid, it was concluded that the efficiency of oxygen transport into and CO.sub.2 transport from the bags was dependent upon the thickness of the bag walls. For a given platelet count, the pH drop of stored concentrates was significantly less for thin walled containers. Concentrates with high platelet counts (2.times.10.sup.6 /mm.sup.3 and greater) stored in standard PVC bags whose walls were considerably thicker had a pH of around 6.0 or lower after three days storage. Murphy and Gardner (Blood, Vol. 35, pp. 549-557, 1970) have also shown that an abrupt loss of in vivo viability occurs if pH falls below 6.0 during storage.
Unfortunately, thicker-walled bags are necessary in the process of obtaining platelet concentrates since the bags are subjected to high speed centrifugation and must be resistant to rupturing. To achieve the degree of flexibility needed for standard PVC bags, the PVC contains a certain percentage of DEHP plasticizer. In the past there has been concern over the possibility of harmful effects on platelets of DEHP which leaches into platelet concentrates stored in standard PVC containers. Although PE contains no plasticizers, it would not be a suitable material for bags in which to collect platelet concentrates any more than thin-walled PVC bags since they are highly susceptible to rupturing during pressure steam sterilization and/or centrifugation.
It would therefore be highly desirable to be able to store platelets in a plastic container having sufficient tensile strength to withstand pressure sterilization and highspeed centrifugation while at the same time having good carbon dioxide and oxygen permeability characteristics so as to prolong platelet survival. It is a particular advantage to prolong platelet survival beyond a three day survival period.
In U.S. Pat. No. 4,280,497 ('497) a plastic container was found which withstands rupturing during pressure heat sterilization and high-speed centrifugation and which had superior characteristics for transmitting carbon dioxide and oxygen. Platelets when stored in such a container maintain acceptable viability for at least five days or longer.
The container of '497 was made in the shape of a bag whose walls were composed of PVC film plasticized with about 30 to about 50 weight percent of tri 2-ethylhexyl trimellitate, preferably about 37 weight percent, and about 3 to 5, preferably about 3.5 weight percent of a heat stabilization system suitable for medical grade PVC plastics such as epoxidized vegetable oils. Typical of the latter were epoxidized soy bean oil and epoxidized linseed oil. Although not critical, the heat stabilization system preferably also included small amounts, i.e., less than one percent, preferably about 0.60 percent, of a metal soap such as zinc stearate, calcium stearate or the like. Very small amounts of a lubricant such as mineral oil could also be included, i.e., less than 0.5 percent.
The blood bag system taught in '379 is a donor bag and transfer bag made of plastic materials which each comprises a different polymer entity. The donor bag is PVC plasticized with DEHP; the transfer bag to be used for platelet storage is made from a material which exhibits relatively high capability to permit the diffusion of carbon dioxide such as the polyolefin-thermoplastic rubber formulation of U.S. Pat. No. 4,140,162. Other transfer bags in the above system may be made of a polyester in accordance with the teachings of U.S. Pat. No. 4,045,431.
It is, however, desirable in the manufacture of blood bag systems to make all of the components, such as the bags, tubing, etc., out of the same material. In this way compatibility of material of each component is assured and manufacturing problems are lessened.
In U.S. patent application Ser. No. 216,098 filed Dec. 15, 1980, there is disclosed an improved multiple blood bag system in which donor as well as transfer bags are made of polymeric substances which are substantially free of blood-extractable plasticizers such as PVC plasticized with tri-2-ethylhexyl trimellitate, polyester, or polycarbonate. The polymeric substance for a donor bag could be the same or different from that of a transfer bag. The polymeric substances were selected so that when whole blood or packed red cells were stored in a donor bag of such material for up to 21 days, the degree of hemolysis was such that the amount of surviving red cells was sufficient for clinical requirements. The polymeric substances also were favorable in the functions for which transfer bags are used such as platelet storage, cryoprecipitate collection and the like.
A polyurethane film is described in United Kingdom Patent Specification No. 1,587,522. The polyurethane film may be used to fabricate blood bags for the removal, storage, deep-freezing, and transfusion of blood and blood constituents.